A broad-spectrum nanobody targeting the C-terminus of the hepatitis B surface antigen for chronic hepatitis B infection therapy

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  • Author: YueWang, YaxianMei, ZhenghongAo, YuanzhiChen, YichaoJiang, XiaoqingChen, RuoyaoQi, BaorongFu, JixianTang, MujinFang, MinYou, TianyingZhang, QuanYuan, WenxinLuo, NingshaoXia
  • Journal: Antiviral Research
  • Doi: https://www.doi.org/10.1016/j.antiviral.2022.105265
  • Publication Date: 2022 Mar

Products/Services used in the paper

Quotation shows PackGene:C57BL/6 mice (Shanghai SLAC Laboratory Animal Co., Ltd., China) were injected with HBV/adeno-associated virus (AAV) (HBV–B from PackGene Biotech, HBV-D from Five Plus Molecular Medicine Institute, China) via the caudal vein. HCAb treatment was conducted as previously described

Research Field:liver

AAV Serotype:HBV–B

Animal or cell line strain:C57BL/6 mice

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Abstract

Sustainable viral suppression with hepatitis B surface antigen (HBsAg) loss is the new treatment goal for chronic hepatitis B (CHB). The role of antibodies in therapies for persistent hepatitis B virus (HBV) infection has received constant attention. While immunotherapy holds great promise, challenges for the antibody-based prevention and control of HBV in CHB include broad HBV antigenic diversity and the need for long-term viral suppression. In this study, we identified a new anti-HBsAg nanobody (Nb), 125s, isolated from HBsAg-immunized alpaca and confirmed its excellent potency in HBsAg clearance and broad-spectrum therapeutic activity against three HBV subtypes in vivo. In addition, we characterized a novel epitope at the C-terminus of the HBsAg surface motif from amino acids 157 to 174. A 125s-based long-term passive immunization program was efficacious at HBsAg clearance and inducing cellular immune responses, offering a promising outlook for CHB immunotherapy.

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